Early-life sex hormone deficiency promotes beneficial remodeling in white adipose tissue and whole-body metabolism

IF 6.4 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2026-02-15 Epub Date: 2026-01-03 DOI:10.1016/j.lfs.2025.124184

Ignacio Miguel , Ana Alzamendi , Alejandro Ezequiel Harnichar , Alejandra Paula Giordano , Carolina Carla Garraza , Eduardo Julio Spinedi , Andrés Giovambattista

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引用次数: 0

Abstract

Aims

This study investigates the impact of female sex hormone deficiency (FSHD) on white adipose tissue (WAT) development, focusing on two distinct depots: retroperitoneal adipose tissue (RPAT) and inguinal adipose tissue (IAT).

Materials and methods

Prepubertal ovariectomy was performed, and animals were pair-fed (FSHD-PF) to account for hyperphagia.

Key findings

FSHD-PF animals exhibited reduced plasma triglyceride and insulin levels, with improved glucose handling. A redistribution of adipose tissue was observed, with increased IAT mass and decreased RPAT mass, accompanied by a reduction in adipocyte size in RPAT. Expression markers of inflammation, such as ob and tnf-α, were significantly decreased in RPAT of FSHD-PF, suggesting a potential reduction in the inflammatory state. Likewise, we found that prepubertal ovariectomy also modulated adipocyte precursor cells (APCs), leading to increased cd34 expression in both depots, indicative of greater competency. However, RPAT showed elevated pparγ-2 levels, while IAT exhibited increased wnt10b, suggesting a depot-specific regulation. Notably, IAT-derived APCs from FSHD-PF animals display enhanced differentiation capacity in vitro. Cold exposure further modulated WAT browning, with a notable increase in UCP-1 protein expression although observed in IAT from FSHD-PF rats only.

Significance

This study is the first to examine FSHD in the context of WAT development, identifying early-life ovarian hormone loss as a critical and previously underexplored determinant of metabolic regulation. Accordingly, the consequences of early FSHD, together with its association with non-shivering thermogenesis, emerge as promising areas for further investigation with potential therapeutic relevance.

Abstract Image

查看原文本刊更多论文

早期性激素缺乏促进白色脂肪组织和全身代谢的有益重塑。

目的：本研究探讨女性性激素缺乏（FSHD）对白色脂肪组织（WAT）发育的影响，重点研究两个不同的部位：腹膜后脂肪组织（RPAT）和腹股沟脂肪组织（IAT）。材料和方法：行青春期前卵巢切除术，并对动物进行配对喂养（FSHD-PF）以解释贪食。主要发现：FSHD-PF动物表现出血浆甘油三酯和胰岛素水平降低，葡萄糖处理能力改善。观察到脂肪组织的重新分布，IAT质量增加，RPAT质量减少，同时RPAT中脂肪细胞大小减少。炎症标志物，如ob和tnf-α在FSHD-PF的RPAT中显著降低，提示炎症状态可能减轻。同样，我们发现青春期前卵巢切除术也会调节脂肪细胞前体细胞（APCs），导致cd34在两个库中的表达增加，表明更强的能力。然而，RPAT显示pparγ-2水平升高，而IAT显示wnt10b水平升高，提示储罐特异性调节。值得注意的是，来自FSHD-PF动物的iat衍生apc在体外表现出增强的分化能力。冷暴露进一步调节WAT褐变，UCP-1蛋白表达显著增加，尽管仅在FSHD-PF大鼠的IAT中观察到。意义：本研究首次在WAT发展的背景下检查FSHD，确定早期卵巢激素损失是代谢调节的关键因素，但以前未被充分探索。因此，早期FSHD的后果及其与非寒颤产热的关联，成为进一步研究的有希望的领域，具有潜在的治疗意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.